Anti-substance P anti-idiotypic antibodies. Characterization and biological activities.

Antibodies to substance P (SP) produced in rabbits have been characterized for their specificity toward SP and some 30 SP-related peptides. For each compound, we observed a close correlation between capacity of binding to anti-SP antibodies and biological activity, namely their spasmogenic effect on guinea pig ileum in vitro and their hypotensive effect in the rat in vivo, indicating that the combining sites of anti-SP and SP receptor(s) are structurally very similar. Further immunization of five rabbits with anti-SP immunoglobulins elicited in two allotype-matched animals the production of anti-SP anti-idiotypic antibodies. These latter antibodies were found to strongly inhibit the spasmogenic action of SP on the guinea pig ileum. In contrast, they specifically enhanced, like SP, phospholipid turnover in rat parotid gland cells, a physiological function mediated through an activation of SP receptors. Immunocytochemical studies actually revealed the presence of specific membranous binding sites for anti-idiotypic antibodies on the parotid gland-dissociated cells. The anti-idiotypic antibodies described here, which thus behave either as agonists or antagonists for SP depending on the biological test, might be used as original and powerful tools not only in studies of the receptor stereospecificity but also in attempts to purify the membranous SP receptors.